McLean SPARED Conte Seed Grant Awards, by year

SPARED Conte Seed Grant Awardee 2022-2023:

Caroline Palavicino-Maggio, PhD Neuroscientist, Assistant Professor of Psychiatry HMS

Investigating the Role of Stress Peptides in Aggression and Sleep in Drosophila

How the nervous system reacts to chronic stress that leads to the selection of changes in aggression and fragmented sleep remains largely unknown. Using the fruit fly model system, we will examine the effects of stress on aggression and sleep duration by manipulating the expression of two highly conserved neuropeptide genes in fruit flies: the mammalian pituitary adenosine cyclase-activating peptide (PACAP) homolog amnesiac (amn) and the corticotropin-releasing factor (CRF) homolog Diuretic Hormone 44 (DH44) . We hypothesize that amn and DH44 are crucial for regulating aggression and sleep. The fruit fly as a model organism offers enormous advantages in these regards because existing powerful genetic methods permit manipulation of small subsets of brain cells and highly conserved genes for exploration of the neural mechanisms of behavior, and we can quantify these behaviors, which may predict what may be happening on a human level. Our study relates to the SEED mission because it focuses on brain peptides implicated in stress responsiveness and their contribution to the development of debilitating illnesses.

SPARED Conte Pilot Award 2022-2023:

Jakob Hartmann, PhD Assistant Neuroscientist, Assistant Professor of Psychiatry HMS

Identification of sex-specific BNST gene networks modulating susceptibility and resilience to chronic stress

Despite the twofold higher prevalence of mood and anxiety disorders in women compared with men, a mechanistic understanding of sex differences in affective disorders is lacking. Mental disorders can develop as a result of gene x environment interactions. However, there is no universal susceptibility gene for such disorders. Instead, multiple genes with small effect sizes may contribute to the disease phenotypes. Moreover, only a subset of individuals is susceptible to adverse experiences (e.g. traumatic stress), while others show resilience. Although the bed nucleus of the stria terminalis (BNST) plays an important role in the stress response and emotional and social behaviors, it has been largely overlooked with respect to its possible sex-specific dysregulation in mental disorders. This proposal aims to investigate sex-specific BNST gene networks modulating susceptibility and resilience to stress by combining state-of-the-art singlecell transcriptomics in animal models with causal chemogenetic tools. The findings generated by these studies have the potential to identify novel therapeutic targets towards the development of new pharmaceutical interventions for use in humans with mental disorders.

SPARED Conte Seed Grant Awardee 2021-2022:

Habiballah Rahimi Eichi, PhD Post-Doctoral Fellow, Department of Psychiatry

Actigraphy-based Standard Biomarker for Stress Triggered Depression

Stressful experiences have been strongly linked to the development of depression; and the depression literature suggests that stressful life events could predict the onset and course of depressive episodes. In this project, I aim to validate an objective actigraphy-based biomarker which models the energy by calculating the physical activity during wake time and immobility during sleep as a measure of sleep quality; and detects the biological stress-triggered depressive episodes as consecutive days of energy conservation mode.

SPARED Conte Pilot Award 2021-2022:

Antonia V. Seligowski, PhD Post-Doctoral Fellow, Department of Psychiatry

Effects of PACAP, CRF, and E2 on cardiovascular physiology in women with PTSD

This proposal will examine the interaction between circulating levels of PACAP, CRF, and estradiol (E2) on three measures of cardiovascular physiology in trauma-exposed women with and without PTSD: 1) blood pressure, 2) flow-mediated dilation (a physiological indicator of endothelial function), and 3) vascular inflammatory markers (blood-based biomarkers of endothelial function). This directly relates to the mission of the SPARED Conte Center by probing the roles of two stress peptides, PACAP and CRF, in PTSD. It also focuses on the sex hormone E2 given that PACAP in particular has sex-specific effects in PTSD, which is twice as prevalent in women compared to men. Further, the risk of cardiovascular disease (CVD) in PTSD is significantly greater than that of the general population, and PACAP, CRF, and E2 have important effects on CVD.

SPARED Conte Seed Grant Awardee 2020-2021:

Suman Guha, PhD Post-Doctoral Fellow, Department of Psychiatry

Anatomically precise nanofluidic sampling and delivery of dynorphin ligands in nucleus accumbens to determine subregions mediating stress-related aversion

Dysregulated neuropeptide systems contribute to stress-related psychopathologies. However, existing tools have not been developed to sample and detect neuropeptide release in interstitial fluid (ISF) during stress with nanometer anatomical precision and accuracy. This proposal uses micro-invasive fluidics platform—developed by Dr. Michael Cima’s laboratory at MIT—to directly measure stress-induced dynorphin release in subregions of the nucleus accumbens shell (NASh), and to micro-deliver a KOR agonist to the dorsal vs ventral NASh to parse out roles of anatomically adjacent regions in stress-related behavior.

Mentor: Elena Chartoff, PhD

SPARED Conte Pilot Award 2020-2021:

Jennifer Fanning, PhD Post-Doctoral Fellow, Department of Psychiatry

Steroid hormones, stress reactivity, and aggression in trauma-exposed adults

More information to come.

SPARED Conte Seed Grant Awardee 2019-2020:

Christos Chatzinakos, PhD Post-Doctoral Fellow, Department of Psychiatry

Neurogenomics & Translational Bioinformatics Laboratory

Computational identification and clinical validation of novel stress peptide biomarkers for PTSD with neurobiological mechanistic relevance

Reliable biomarkers to pinpoint the development and pathophysiology of PTSD are lacking. This proposal seeks to computationally identify and clinically validate stress peptide (SP) biomarkers in PTSD. He will identify and clinically validate statistically reliable SPs based on: membership or regulation in amygdala gene networks, brain-to-plasma genetic correlation, and genetic association with PTSD.

Mentor: Nikolaos Daskalakis, MD, PhD